2.A.1.2.57 MFS-type polyamine transporter SLC18B1 or VPAT (Solute carrier family 18 member B1) of 456 aas and 12 TMSs. Polyamines synthesized in neurons and astrocytes are stored in secretory
vesicles and released upon depolarization. Vesicular storage
is mediated in an ATP-dependent, reserpine-sensitive process. SLC18B1 is the fourth member of the SLC18 transporter family, which includes
vesicular monoamine transporters and a vesicular acetylcholine
transporter. Proteoliposomes containing purified human SLC18B1 protein actively transport spermine and spermidine in exchange of H+. The SLC18B1 protein is predominantly expressed in the hippocampus and is associated with vesicles in astrocytes. SLC18B1 gene knockdown decreased both the amount of the SLC18B1 protein and the spermine/spermidine contents of astrocytes (Hiasa et al. 2014). Slc18b1 knock out mice have reduced polyamine content in the brain These mice have impaired short and long term
memory in novel object recognition, radial arm maze and
self-administration paradigms (Fredriksson et al. 2019). Moreover, Slc18b1 KO mice have
altered expression of genes involved in Long Term Potentiation,
plasticity, calcium signalling and synaptic functions, and expression of components of GABA and glutamate signalling are alterred. These mutants show partial resistance to diazepam, manifested as lowered reduction in locomotion after diazepam treatment.
Possibly, removal of Slc18b1 leads to reduction of polyamine
contents in neurons, resulting in reduced GABA signalling due to
a long-term reduction in glutamatergic signalling (Fredriksson et al. 2019).
|
Accession Number: | Q6NT16 |
Protein Name: | MFS-type transporter SLC18B1 |
Length: | 456 |
Molecular Weight: | 48869.00 |
Species: | Homo sapiens (Human) [9606] |
Number of TMSs: | 12 |
Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
Substrate |
|
---|
Entrez Gene ID: |
116843
|
Pfam: |
PF07690
|
KEGG: |
hsa:116843
|
|
[1] “Complete sequencing and characterization of 21,243 full-length human cDNAs.” Ota T. et.al. 14702039
[2] “The DNA sequence and analysis of human chromosome 6.” Mungall A.J. et.al. 14574404
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).” The MGC Project Team et.al. 15489334
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1: MEALGDLEGP RAPGGDDPAG SAGETPGWLS REQVFVLISA ASVNLGSMMC YSILGPFFPK
61: EAEKKGASNT IIGMIFGCFA LFELLASLVF GNYLVHIGAK FMFVAGMFVS GGVTILFGVL
121: DRVPDGPVFI AMCFLVRVMD AVSFAAAMTA SSSILAKAFP NNVATVLGSL ETFSGLGLIL
181: GPPVGGFLYQ SFGYEVPFIV LGCVVLLMVP LNMYILPNYE SDPGEHSFWK LIALPKVGLI
241: AFVINSLSSC FGFLDPTLSL FVLEKFNLPA GYVGLVFLGM ALSYAISSPL FGLLSDKRPP
301: LRKWLLVFGN LITAGCYMLL GPVPILHIKS QLWLLVLILV VSGLSAGMSI IPTFPEILSC
361: AHENGFEEGL STLGLVSGLF SAMWSIGAFM GPTLGGFLYE KIGFEWAAAI QGLWALISGL
421: AMGLFYLLEY SRRKRSKSQN ILSTEEERTT LLPNET